Engineered Bacteriophage T7 as a Potent Anticancer Agent in vivo

Area of Science:

• Oncolytic virotherapy
• Bacteriophage engineering
• Cancer immunotherapy

Background:

• Oncolytic viruses (OVs) offer dual mechanisms for tumor destruction: direct cell lysis and immune stimulation.
• Bacteriophages, as bacterial pathogens, present safety and production advantages over human viruses for therapeutic applications.

Purpose of the Study:

• To engineer a bacteriophage T7 to target murine melanoma cells and express granulocyte macrophage-colony stimulating factor (GM-CSF).
• To evaluate the efficacy of the engineered bacteriophage in inhibiting tumor growth and modulating the tumor microenvironment in vivo.

Main Methods:

• Construction of an engineered bacteriophage T7 displaying a peptide targeting murine melanoma and carrying a GM-CSF expression cassette.
• In vitro and in vivo transduction of B16F10 melanoma cells with the engineered phage.
• Assessment of tumor growth inhibition, survival rates, serum cytokine levels, and immune cell infiltration in treated mice.

Main Results:

• The engineered phage successfully transduced melanoma cells and expressed GM-CSF.
• Intravenous phage treatment significantly improved mouse survival and inhibited tumor growth by 72%.
• Phage therapy increased serum levels of IL-1α, TNF-α, and GM-CSF, and promoted infiltration of macrophages, dendritic cells, and CD8+ T cells into tumors.

Conclusions:

• Recombinant bacteriophage T7 effectively inhibits melanoma tumor growth by altering the tumor microenvironment.
• The engineered phage recruits anti-tumor immune cells, suggesting its potential as a novel cancer immunotherapy agent.